PROJECT SUMMARY Osteoarthritis (OA) is a leading cause of functional disability in the United States and worldwide. Premature development of knee OA is recognized with increasing frequency in young adults after anterior cruciate ligament (ACL) reconstruction (ACLR). As early as 7 to 15 years following reconstruction, a large majority of individuals develop knee OA, a major cause of pain, functional disability and decline in quality of life throughout the adult life-span. In line with the mission of the National Institute of Arthritis and Musculoskeletal and Skin Diseases, this proposal will advance knowledge into the causes, treatment, and prevention of knee OA and related disability after ACLR. The long-term objective of our team is to improve the current model of care for patients after ACLR. This prospective study will provide critical data needed to inform an effective future clinical trial. The proposed Aims incorporate multimodal testing of outcomes following ACLR. Through the proposed aims, we will obtain critical knowledge to guide our future clinical trial.